Mark Rose

Mark Rose

Mark Rose

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The authors find that CTP-synthase forms filaments in yeast and Drosophila cells. In a remarkable synchronicity of research findings, a paper showing that CTP-synthase forms filaments that can regulate cellular morphology in bacterial cells was also just published {1}.In both papers, genome-wide screens of GFP-tagged proteins identified novel filament-forming proteins. In this paper, the authors identified 9 proteins that assemble into 4 independent filaments. These 4 filaments include several proteins involved in protein elongation as well as the now ubiquitous CTP-synthase. Furthermore, the formation of each type of filament was under differential regulation. For example, depletion of glucose or reaching the stationary phase favored CTP-synthase filament formation, whereas treatment with cycloheximide inhibited elongation-factor filament formation. The authors show that treatment with high concentrations of CTP and ATP increases filament formation, consistent with the idea that the filaments may represent an inactive storage assembly. The very widespread finding of CTP-synthase forming filaments further supports the idea that this structure has been co-opted into a morphogenesis role in Caulobacter {1}.

John Wallingford

John Wallingford

John Wallingford

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This paper identifies several new proteins that form filaments in the cytoplasm of eukaryotic cells, essentially doubling the number of filament systems (and thus potentially the number of cytoskeletal elements).The authors find that several enzymes and translational machinery components assemble into filaments in yeast cells. These filament systems are largely non-overlapping. As a developmental biologist, the variety of filaments formed by CTP synthase in various cell types was to me the most fascinating aspect. In the Drosophila ovary, networks of filaments were present in most cells, while each nurse cell also contained a single, very large filament. Moreover, in neurons, CTP synthase filaments were present in axons, but not in dendrites. The authors propose that such filament forming activity is a form of compartmentalization and is related to control of these enzymes’ activities. Given that many proteins serve double-duty, it is also an attractive hypothesis that these filaments may serve a cytoskeletal function. Indeed, a cytoskeletal role for CTP synthase has just been shown in bacteria {1}.

Mohan Balasubramanian

Mohan Balasubramanian

Mohan Balasubramanian

Mithilesh Mishra

Mithilesh Mishra

Mithilesh Mishra

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In a fascinating discovery, the authors identify novel proteins that are capable of organizing into intracellular filamentous structures. Strikingly, the authors find that filamentous structures of the enzymatic protein CTP (cytidine triphosphate) synthase are conserved from yeasts to mammals and that, together with the finding by Ingerson-Mahar et al. {1}, this feature seems to be conserved in bacteria as well.

The authors of this paper screened a yeast GFP (green fluorescent protein) library to find new proteins that were capable of organization into supramolecular structures and identify nine proteins, of which four form filamentous structures. The authors further characterize CTP synthase and show that filament formation is a conserved feature in Drosophila and mammals, albeit that, in mammals, it is restricted to neurons. Relying on previous extensive biochemical analysis on the protein, the authors show that the end-product inhibition of the enzymatic activity stimulates filament assembly. The spatial organization of CTP synthase and its restriction to the axons in the neurons suggests additional functions for the assembly into filaments that are distinct from its enzymatic regulation. It will be of immense interest in the future to see in what other ways eukaryotes have evolved and adapted the filament-formation ability of this enzyme, CTP synthase (akin to the localization to inner curvature of the cell and adaptation to regulate cell morphology in the bacteriumCaulobacter crescentus {1}).

William Sullivan

William Sullivan

William Sullivan

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Remember the biochemical pathways memorized as undergraduates? One issue never addressed was location. That is, where are the enzymes driving these processes located in the cell? By directly addressing this issue, Noree and colleagues have identified four entirely unsuspected eukaryotic filament systems. These filaments, all enzymatically based, were identified by screening the yeast green fluorescent protein (GFP) strain collection. Cytidine triphosphate (CTP) synthase filaments were shown to be conserved in yeast and Drosophila. They are restricted in axons in neurons, suggesting roles in addition to their enzymatic activity. They also demonstrated that filament formation is linked to enzyme activity. These studies are particularly exciting as they suggest new mechanisms for organizing and regulating biochemical pathways in the constantly changing environment of the eukaryotic cytoplasm.